1. Field of the Invention
This invention is directed to a method of the synthesis of D-myoinositol-1-phosphate commonly accepted as a metabolic intermediate for inositol-1,4,5-triphosphate.
2. Description of the Prior Art
Inositol-1,4,5-triphosphate has of late enjoyed credit as a second messenger of information in a cellular system of human beings. This has led to extensive research on the physiological activity and mechanism of and the pharmaceutical effect of inositol-1,4,5-triphosphate and its metabolites.
Inositol-1,4,5-triphosphate is restrictedly available from organisms as it is less isolable in pure form on hydrolysis and extraction and rather existent in only appreciable content. Many attempts have been made to cope with this problem to obtain such inositol triphosphate via chemical synthesis as taught by M. J. Berridge et al., Nature 306, 67 (1983) and ibid., 312, 315 (1984). In 1985 inositol-1,4,5-triphosphate was successfully synthesized from myoinositols by S. Ozaki, one of the present inventors, and his colleagues as reported by S. Ozaki et al., Terahedron Lett., 27, 3157 (1986).
Myoinositols useful as the starting materials are liable to necessarily form equimolar enantiomers in the course of synthesis. This is due to the myoinositols being of a meso type in nature. To obtain inositol-1,4,5-triphosphate of optical activity, a given myoinositol is required to be optically resolved, for example, by a method in which a racemate is reacted with an optically active compound to synthesize a diastereomer, followed by separation of the same as on column chromatography, or by a method in which a racemic compound is separated with use of a suitable column. Optical resolution, however, has a drawback in that it tends to invite decreased product yield and reduced operation efficiency.
It has also been proposed that inositols of optical activity be synthesized with use of optically active starting material, hence without resort to optical resolution, as disclosed by S. Ozaki et al., J. Org. Syn. Chem., Japan, 47, 363 (1989). This prior mode of synthesis has been found too tedious in operation and too low in yield to warrant commercial application.
A keen demand has been voiced, though quite recently, for chemical syntheses of inositol-1,4,5-triphosphate and its metabolites. In addition to inositol-1,4,5-triphosphate, certain other inositol phosphates have been synthetically obtained in which are included inositol-2,4,5-triphosphate, inositol-1,3,4,5-tetraphosphate and inositol-1,3,4-triphosphate, the latter two compounds being regarded as metabolic products for inositol-1,4,5-triphosphate.
D-Myoinositol-1-phosphate is accepted in the art as a metabolic intermediate for inositol-1,4,5-triphosphate and as a physiologically active material. However, insufficient availability leaves much unsolved with respect to the effect of the intermediate. The only one method known to synthesize D-myoinositol-1-phosphate is disclosed by the Merch group, D. A. Billington et al., J. Chem. Soc., Chem. Commun., 314 (1987). The Merch method involves the use of optical resolution, leading to the foregoing difficulties.
Myoinositol-1-phosphate of an L type can be synthesized from L-quebrachitol as reported by S. D. Gero, Tetrahedron Lett., 25, 5681-5687 (1989).